Efficacy of Fractional 2940-nm Erbium: YAG Laser Combined with Platelet-Rich Plasma Versus its Combination with Low-Level Laser Therapy for Scar Revision

J Clin Aesthet Dermatol. 2024;17(11):39–44.

by Mai Abdelraouf Osman, MD, PhD; Nevien Ahmed Samy, MD, PhD; and Ahmed Shami Jasim, MSc

Drs. Osman and Samy are with the National Institute of Laser Enhanced Sciences (NIlES) in Giza Governorate, Egypt. Dr. Jasim is with the Burn Center at Fallujah Teaching Hospital in Al Anbar Governorate, Iraq.

FUNDING: No funding was provided for this article. 

DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article.

ABSTRACT: Objective: We sought to compare the safety and efficacy of combining fractional 2940-nm Erbium:YAG (Er:YAG) laser with autologous platelet-rich plasma (PRP) versus its combination with low-level laser therapy (LLLT) for enhancing the outcome of postsurgical and post-traumatic scars.

Methods: Forty-five individuals with post-surgical or post-traumatic scars were randomly divided into three groups: Group A received four fractional Er:YAG laser sessions spaced four weeks apart along with eight sessions of intradermal PRP injections spaced two weeks apart; Group B received four fractional Er:YAG laser sessions spaced four weeks apart along with two sessions of light emitting diode (LED) weekly; and Group C received four fractional Er:YAG laser sessions spaced four weeks apart. Treatment efficacy was evaluated using clinical photographs, Vancouver Scar Scale (VSS), patient satisfaction and histopathology.

Results: Regarding vascularity following treatment and the total VSS score, there were significant differences between the studied groups, with scoring was the lowest in Group A compared to Group B and C. Patient satisfaction was the highest in Group A compared to Group B and C. Limitations: A limitation of the current study is the short follow-up period.

Conclusion: Scar revision therapy using combined fractional Er:YAG laser with either PRP or LLLT were found to be more efficient and superior to fractional Er:YAG laser alone.

Keywords: Fractional Er:YAG laser, PRP, low-level laser therapy, scar revision

Introduction

Scars are a result of fibrosis and changes in skin morphology during the healing of cutaneous wounds. All wounds heal to some extent with the production of scars, and many scar forms can develop following surgery, trauma, and inflammatory disorders of the skin. Patients who have scars may experience substantial cosmetic, bodily, and psychological effects, leading many to seek treatment. Many types of scars can resolve with treatment, and there is a growing evidence that using lasers can help reduce keloids, atrophic, hypertrophic, and acne-related scars, among others.^1,2

The capacity of laser devices has improved due to recent advancements in laser technology to improve the appearance, texture, and pliability of a variety of scars. In order to encourage eventual remodeling of dermal collagen and elastin, laser scar revision targets intra- and extracellular components within scar tissue. There have been many lasers used to treat scars since the 1980s, starting with continuous-wave argon, carbon dioxide (CO₂) laser, and Nd:YAG 1064 lasers and progressing to the use of pulsed dye laser (PDL) and Er:YAG lasers for scar revision. Scars can now be effectively treated with fractional photothermolysis using both ablative and non-ablative fractionated lasers.³ 

Fractional 2940-nm Er:YAG laser targets both the epidermis and dermis through columns of thermal damage known as microscopic thermal treatment zones (MTZs) that are separated by surrounding untreated skin.⁴ 

Currently, there is some indication that platelet-rich plasma (PRP), an autologous blood-derived product that is high in platelets, growth factors, and chemo/cytokines and given in a concentrated volume of plasma, may lessen the duration of side effects from fractional laser therapy and enhance the appearance of depressed acne scars. PRP can also enhance outcomes when combined with fat grafting and fractional laser resurfacing for the revision of traumatic scars, healing parameters, and early scar quality after a cesarean delivery.⁵

 Low-level laser therapy (LLLT) is an evolving medical procedure used to treat a wide range of illnesses that call for promoting healing, reducing pain and inflammation, and regaining function. LLLT is used as a preventative measure to change the way wounds heal in order to prevent or lessen the development of keloids or hypertrophic scars after scar revision by surgery or CO₂ laser ablation.^6,7 

The aim of the current study was to compare the efficacy and safety of fractional Er:YAG laser combination with either PRP or diode laser in the treatment of post-surgical and post-traumatic scars.

Methods

This comparative, prospective, single-blinded, randomized study included 45 patients (29 female and 16 male) with linear slightly elevated and/or erythematous postsurgical or post-traumatic scars. The study was conducted from the beginning of March 2022 until the end of April 2023.

Each group (A, B, C) comprised 15 patients created by randomly dividing eligible participants. Group A was given four fractional Er:YAG laser sessions spaced four weeks apart, combined with eight sessions of intradermal PRP injection treatments spaced two weeks apart. Group B was given four fractional Er:YAG laser sessions at four-week intervals combined with LED/diode laser sessions twice weekly for three months. Group C was given four fractional Er:YAG laser sessions alone, spaced four weeks apart.

Exclusion criteria included patients with bleeding tendency, any acute infection, platelet dysfunction, autoimmune disorders, immunosuppressive medication users, patients who recently used oral retinoid medications, pregnant or nursing participants, and patients who had prior cosmetic operations, such as dermabrasion, chemical peels, laser resurfacing, botulinum injections, or filler injection prior to the trial.

Ethical approval. Prior to enrollment, informed, written consent with explanations was obtained from each patient. A documented approval from the Research Ethical Committee of National Institute of Laser Enhanced Sciences (NILES-EC-CU-24-3-7) was obtained. The Helsinki Declaration of 1975 guided the conduct of this clinical investigation.

Laser parameters. Five passes of fractional Er:YAG laser (Fotona Xs dynamics, Ljubljana Slovenia) were made over the scar areas in vertical, horizontal, and diagonal directions. All patients were treated using the same device settings. Using the parameters of energy of 600mJ in micro-short pulse mode (MSP), spot size of 7mm, and frequency of 5Hz, the first pass was performed over the entire area. The second pass was applied over the scar area with the same settings. The third pass was applied over the entire region with the following parameters: energy of 1,000mJ in short pulse mode (SP), spot size of 7mm, and frequency of 5Hz. The fourth pass was solely used on the scar area and had the following specifications: energy of 1,200mJ in short pulse mode (SP), spot size of 7mm, frequency of 5Hz. The fifth pass was applied on the scar area with the following specifications: energy of 1,500mJ, extra-long pulse mode (XLP), spot size of 7mm diameter, and frequency of 5Hz.

A LLLT 810-nm diode laser (ELT diode laser 810-nm, Cairo, Egypt) was used on the scar tissue with the following parameters: Power output 250mW, energy density 12 J/cm and irradiation time 50 seconds. Sessions were administered twice per week over 12 consecutive weeks with a total of 24 sessions.

PRP preparation and injection. Venous blood (10mL) was collected in sterile tubes with sodium citrate 3.8% after being drawn under sterile circumstances. Every tube was centrifuged for seven minutes at 2,000rpm. The plasma and buffy coat were carefully removed in every tube, and the contents were transferred to an additional, simple tube without an anticoagulant. The plasma was split into two parts, with the lower part being PRP and the top part being platelet-poor plasma (PPP), after a second cycle of centrifugation, this time at 4,000rpm for 7 to 10 minutes. Blood platelet concentrations were typically between 200,000 and 5,000/lL. A platelet concentration of more than one million/lL equivalent to 4 to 7 times usual values is generally acknowledged as an appropriate therapeutic concentration, even if the platelet count of PRP has not been adjusted.⁸ Using an aseptic approach and a disposable 27-gauge needle, PRP was injected into scars. Over the course of three months, treatments were given once every two weeks for a total of eight sessions. All patients that underwent laser treatment were followed-up for a period of three months after the end of the treatment period, in order to note the final result of the appearance of scars after treatment.

Study assessment. Photography. Standardized high-resolution digital photographs were taken with the same camera settings (Samsung, Seoul, South Korea) before the commencement of therapy, and three months following the final therapy session. An independent dermatologist who was blinded to the study protocol used pre- and post-photographs to evaluate the clinical improvement. 

Vancouver Scar Scale (VSS). This scale consists of four physician-reported parameters to score the skin appearance: pigmentation (0–3), vascularity (0–3), pliability (0–5), and height (0–3).⁹ Total score ranges from 0 to 14 points, with 0 representing normal skin appearance, while maximum scores indicate the worst possible outcome. VSS was measured before and three months following the last treatment. 

Patient satisfaction. On a four-point scale, patient satisfaction was rated as: 4 (very satisfied), 3, (satisfied), 2 (neutral), and 1 (dissatisfied). In addition, patients were asked to note any unpleasant cutaneous reactions or complications each time they visited the physician and during the three-month follow-up.

Histologic assessment. A punch biopsy (2–3mm) was obtained from scar tissue before and three months after the last treatment for histologic analysis. For a quantitative assessment of collagen, biopsy tissues were embedded in paraffin and 10% buffered formalin for fixing. Hematoxylin and eosin (H&E) stain was applied to sections of the paraffin blocks that were 7mm thick. 

Statistical analysis. The US-based SPSS program version 18 was used to analyze the data. Data presented as a mean ± SD and median (min-max). For parametric data, one-way analysis of variance (ANOVA) was used for the statistical comparisons, while for non-parametric data, Wilcoxon signed rank test and Kruskal-Wallis were used. Frequency and percentage were used to illustrate categorical data. Additionally, a comparison was conducted using chi-square or Fisher exact methods. The degree of importance will be determined at P≤0.05.

Results

A total of 45 patients divided randomly into three equal groups (A, B and C) completed the treatment course and the follow-up period. There was no significant difference regarding clinico-epidemiologic details of the studied groups as shown in Table 1.

There was a significant difference in vascularity, height, pliability, pigmentation, and total score between before and after treatment in each studied group. Regarding vascularity after treatment, there was a significantly better improvement in Group A compared to Group C (P2=0.006). In addition, the total VSS score was significantly the lowest in Group A compared to Group B and Group C (P1=0.04, P2=0.0001) respectively. On the other hand, the total scar score was lower in Group B than Group C. However, this difference was not significant (P3=0.22) (Table 2).

Histopathologic evaluation by H&E staining revealed broad interfibrillar spaces and dense disorganized dermal collagen bundles in untreated scar tissue. At three-month follow-up, the collagen bundles became less dense and more organized with scattered spindle-shaped fibroblasts in the papillary dermis in all studied groups (Figures 1–3). 

Regarding patient satisfaction, the highest percentage of patient satisfaction (very satisfied and satisfied) was in Group A (fractional Er:YAG laser +PRP) compared to Group B (fractional Er:YAG laser+diode laser) and Group C (fractional Er:YAG laser alone) (Table 3).

Regarding side effects, mild-to-moderate erythema was reported in all studied groups with the highest percentage in Group A (93.3%) compared to Group B (66.7%) and Group C (46.7%) (p= 0.02). Itching was reported in Group B and Group C only; however, the difference was not significant (p=0.43). No serious adverse effects such as post-inflammatory hyperpigmentation or blistering were observed in any patient. No patient reported any interference in his/her daily activities in the immediate post-treatment period.  

Discussion

Most scars have pigmentary abnormalities, surface irregularities, and abnormal vasculature. Fractional ablative lasers have demonstrated efficacious in treating, and favorably altering, all of these aberrant scar characteristics. The clear understanding of which laser should be used and which regimen to be adopted is paramount in order to obtain the utmost benefit while enabling patients to return more closely to their premorbid state.¹⁰ To our knowledge, this is the first study to compare and evaluate fractional Er:YAG laser combined with PRP versus its combination with diode laser for the treatment of scars over a three-month follow-up period, using VSS, blinded photo evaluation, patient perspectives, and histopathology.

The current work demonstrated a significant improvement in scar quality and aesthetic outcome of all studied groups irrespective of treatment modality. The positive effects on patients’ viewpoints could further substantiate these results. Besides, histologic improvements were found to correlate with clinical efficacies as evidenced by H&E staining.

In the present study at three-month follow-up, the vascularity score was the highest in Group C. However, the difference was only significant in Group A (Er:YAG laser + PRP) versus Group C (Er:YAG laser alone). Similarly, Group C recorded the highest score regarding the total VSS, but the difference was only significant in Group A versus Group B and in Group A versus Group C.

Fractional ablative lasers deliver laser beam in a fractionated pattern while leaving areas of surrounding tissue untouched. These tiny columns of thermal injury are believed to evoke a molecular cascade that promote collagen remodeling and scar regression. Confluent epidermal damage is thus avoided and quicker healing and reepithelialization is allowed. This is important for scars where the distorted normal anatomy has sparse epidermal appendages to act as a storage of regenerative stem cells.¹¹ 

Er:YAG laser with a wavelength of 2940-nm emits light in the near infrared region and can achieve superficial tissue ablation due to its great affinity for intracellular water which is 12 times higher than that of the CO₂ laser.¹² 

Prior studies have evaluated fractional ablative Er:YAG laser for the treatment of scars. Tidwell et al¹³ enrolled 20 patients in a split-scar study comparing fully ablative Er:YAG laser with fractional Er:YAG laser. The scars were treated at monthly intervals for three months and followed up at Months 1 and 2 after the last treatment. A statistically significant superior outcome in fractional Er:YAG laser over fully ablative Er:YAG laser was documented and the patients preferred the fractional Er:YAG laser compared to the fully ablative laser when asked at the end of the study.

PRP has the ability to rebuild lost collagen and elastic fibers ameliorating the appearance of scars through the release of several growth factors from their α-granules such as platelet-derived growth factors (PDGF), transforming growth factors (TGF), insulin-like growth factor (IGF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). These growth factors promote the growth of human adipose-derived stem cells, type 1 collagen, and human-derived fibroblasts in addition to enhancing cell differentiation, proliferation, and regeneration.¹⁴

In the present study, combining fractional Er:YAG laser with either PRP or diode laser exhibited better results compared to fractional Er:YAG laser alone. This could be accredited to the synergistic impact of using two treatment modalities together. This finding was verified by a study done by El-Taieb et al¹⁵ who demonstrated that when PRP and Er:YAG laser were employed together, the overall improvement of acne scars was much higher than that obtained with either line alone (P=0.001). 

A recent study by Dai et al¹⁶ showed that PRP is an effective adjunct for ablative fractional CO₂ laser in the treatment of hypertrophic burn scars and that this combination regimen proved to be more useful than fractional CO₂ laser alone. 

LLLT acts by stimulating collagen synthesis thus improving the quality and quantity of the scar tissue. Another mechanism of action includes enhancement of microcirculation which can speed up the healing process. Indeed, LLLT also enhances cell and tissue repair through stimulation of mitochondrial oxidative metabolism.¹⁷

The role of LLLT in the treatment of scars has been supported by previous studies which were in fact conforming to the results of the current study. Freitas et al¹⁸ reported a positive effect on the appearance of macroscopic scars, and on the thickness of old scars in 17 volunteers after 15 sessions of LLLT. 

Likewise, in a randomized, controlled study involving 28 patients who underwent surgery for inguinal hernias, LLLT (830-nm) appeared to be effective in preventing the formation of keloids and resulted in better scar appearance and quality six months after surgery.¹⁹ 

In the current study, mild-to-moderate erythema was the only common side effect among the three studied groups, while itching was noted in Group B and Group C only. No substantial side effects, that require discontinuation of treatment were found. Similar research documented the safety of fractional Er:YAG laser, PRP, and diode laser in the treatment of scars with minimal side effects.^20–22 

Limitations. A limitation of the current study was the short follow-up period. Since scar remodeling continues after a lapse of time, further improvement might be expected with longer follow-up period.

Conclusion

For scar revision, combined fractional Er:YAG laser approach with either PRP or diode laser were found to be more efficient and safer than fractional laser treatment alone with improved outcomes and patient satisfaction. Moreover, combined fractional Er:YAG laser with PRP has surpassed its combination with LLLT for the correction of scars. Nevertheless, additional comparative controlled studies with long-term follow-up are still needed to confirm these findings.

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